Primary mediastinal lymphoma: diagnosis and treatment options

Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) is a unique B-cell lymphoma variant that arises from a putative thymic medulla B cell. It constitutes 2–4% of non-Hodgkin lymphomas and occurs most frequently in young females. PMBCL is characterized by a diffuse proliferation of medium-to-large B cells associated with sclerosis. Molecular analysis shows that PMBCL is a distinct entity compared to other types of diffuse large B-cell lymphomas. PMBCL is characterized by a locally invasive anterior mediastinal bulky mass. The combination of rituximab with CHOP/CHOP-like regimens followed by mediastinal radiation therapy (RT) is associated with a 5-year progression-free survival of 75–85%. However, the role of consolidation RT still remains uncertain. More intensive regimens, such as DA-EPOCH-R without mediastinal RT, have shown very promising results. The conclusive role of PET-CT scan requires prospective studies and there is hope that this may allow to de-escalate RT and accordingly yield reliable prognostic information.

Keywords:

• chemotherapy
• histopathology
• International Prognostic Index
• JAK-STAT pathway
• PET-CT scan
• primary mediastinal lymphoma
• programmed death ligand
• radiotherapy
• rituximab
• third-generation regimen

Acknowledgements

The authors are grateful to S Pileri and D Rossi for scientific contributions and O Bagni (Nuclear Medicine Latina) for the clinical and diagnostic PET-CT support.

Financial & competing interests disclosure

This work was endorsed by the Italian Lymphoma Foundation. M Martelli reports grants and personal fees from Roche, Mundipharma and Celgene. R Foà reports grants and personal fees from Roche, Genentech, Janssen, Gilead, Amgen and Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinical and biological entity from other types of diffuse large B-cell lymphoma (DLBCL).

• PMBCL has a better outcome compared to other nodal DLBCL probably related to younger age and localized disease.

• Rituximab combination with CHOP/CHOP-like regimens could nullify the differences with more intensive third-generation regimens (e.g., V/MACOP-B).

• R-CHOP/CHOP-like and MACOP-B/VACOP-B therapies with consolidation mediastinal RT in selected patients should be considered as the standard treatment.

• DA-EPOCH-R without mediastinal radiation therapy has shown very promising results, but this therapeutic advance needs to be confirmed in further prospective trials.

• The rate of post treatment PET positivity is higher than in other DLBCL, using the mediastinal blood pool cut-point; however, post-treatment negative PET-computerized tomography is significantly associated with a better survival.

• The liver uptake according to Deauville visual analysis may represent a more appropriate cut-point to identify patients with increased risk of relapse.

• The real role of consolidative mediastinal radiotherapy needs to be better assessed in prospective comparative studies.

• Recent investigations have brought new insight into the molecular mechanisms that contribute to the malignant phenotype of PMBCL and this may lead to a future development of targeted therapies.

Notes